Field of the Invention
This invention relates to the preparation of a herpesvirus subunit vaccine, and in particular to a Herpes simplex type 1.
Herpesviruses are ubiquitous in nature; hatural hosts include the frog, chicken, mouse, guinea pig, cat, dog, swine, cow, horse, monkey and man. Man is the natural host for Herpes simplex type 1 varicella/zoster, cytomegalovirus and Epstein-Barr. Clinical illness caused by herpes viruses presents a significant health problem for which no effective preventive measures are available. Herpes simplex type 1 (HSV1)is transmitted by the oral-respiratory route and is most frequently associated with oral lesions.
Members of the herpesvirus group are relatively large enveloped ether-sensitive DNA viruses. Herpes simplex type 1 viruses have been shown characteristically to contain two predominant molecular weight groups of envelope glycoproteins.
Herpesviruses present unique and individual problems for vaccine development, especially for use in man. Generally, viral vaccines, whether live attenuated vaccines or killed inactivated vaccines, are prepared from virus contained in animal host fluids or cell culture fluids or viral concentrates derived therefrom. However, herpesviruses in general tend to be more cell-associated than many other viruses, i.e., do not shed into the fluids, and, especially some members of the group, do not propagate readily to the high level of virions required for large scale manufacture of vaccine. Additionally, certain herpesviruses are suspected of being oncogenic for man. Preparation of vaccines from such viruses presents a special problem in that the vaccine must be free of any viral genetic information capable of inducing cancer. Even inactivated whole virus vaccines are viewed as potentially hazardous in such cases because they contain viral nucleic acid. Recently, efforts toward improved viral vaccines have lead to the development of subunit or "split" vaccines to reduce or remove unwanted host or viral components in the vaccines. An example in point is the preparation of influenza viral subunit vaccine from infected chick egg allantoic fluid to reduce the toxicity and pyrogenicity as described in U.S. Pat. No. 3,962,421. However, such subunit vaccines have not emphasized or demonstrated the removal and/or deactivation of viral genetic information as will be needed for viruses suspected of playing an etiologic role in cancer.